Studies have revealed that smarca5 promotes the development of embryonic hematopoietic stem progenitor cells

Hematopoiesis can produce all types of blood cells, including red blood cells, platelets, macrophages and lymphocytes. These blood cells are derived from hematopoietic stem progenitor cells with self-renewal and multi-directional differentiation potential. In vertebrates, the earliest hematopoietic stem progenitor cells are produced by the blood producing endothelium on the ventral side of the artery in the aortic gonad mesorenal region through the process of endothelial hematopoietic transformation. Hematopoietic stem progenitor cells migrate to mammalian fetal liver or tail hematopoietic tissue of zebrafish for rapid expansion and differentiation. It has been found that the hematopoietic stem progenitor cells (HSCs) just produced in AGM region of mice are in an immature state. Only when hematopoietic stem progenitor cells migrate to fetal liver, can they fully acquire hematopoietic related transcriptome characteristics. In addition, the ability of hematopoietic stem cells from AGM and fetal liver is different: hematopoietic stem cells produced in AGM region are more sensitive to immune rejection and can only be transplanted into newborn mice. Therefore, the study of hematopoietic stem progenitor cells in different stages of development and the comparison of their chromatin opening status and gene regulation differences will provide theoretical guidance for the in vitro induction of hematopoietic stem progenitor cells with good transplantation reconstruction ability. < p > < p > on August 5, Liu Feng, a researcher at the Institute of zoology, Chinese Academy of Sciences, and Zhang Yong, Professor of Tongji University, published a research paper entitled smarca5 mediated epigenetic programming facilities, total thermopoietic stem and generator cell development in vertebrates, on bloom. It has been found that chromatin accessibility and transcriptome change dynamically in hematopoietic stem progenitor cells at different developmental stages, such as generation, amplification / differentiation. In depth mechanism exploration found that smarca5 interacts with nucleolin to promote chromatin remodeling and regulate the binding of hematopoietic related transcription factors with genome, thus promoting the development of hematopoietic stem progenitor cells. < / P > < p > using zebrafish as a model animal, the researchers focused on chromatin accessibility and transcriptome to study the dynamic regulation of gene expression of hematopoietic stem progenitor cells in two hematopoietic tissues during embryonic stage. ATAC SEQ and RNA SEQ were used to analyze the newly generated hematopoietic stem progenitor cells (HSCs) in AGM region and CHT region of zebrafish at the stage of amplification / differentiation. It was found that the chromatin openness in AGM region and CHT region had dynamic changes, and the chromatin opening degree in promoter region had more obvious effect on gene transcription. Compared with the hematopoietic progenitor cells, the hematopoietic progenitor cells were more enriched in the hematopoietic progenitor region. At the same time, the expression level of hematopoietic related genes was higher in hematopoietic stem progenitor cells in CHT region. These results suggest that hematopoietic stem progenitor cells in CHT region have more stable and specific hematopoietic capacity. < / P > < p > in order to find the key chromatin remodeling factors that regulate the changes of chromatin status during the development of hematopoietic stem cells, the researchers combined the expression of chromatin remodeling factors in AGM and CHT regions and gene knockout / knockout experiments to confirm that smarca5 promotes the proliferation and differentiation of hematopoietic stem progenitor cells in CHT area by regulating chromatin accessibility. In addition, through mass spectrometry and functional experiments, the researchers found that nucleolin could interact with smarca5 and regulate the expansion / differentiation of hematopoietic stem progenitor cells in the CHT region. Further mechanism studies have shown that nucleolin contributes to smarca5 mediated chromatin remodeling, and then affects the binding of transcription factors related to the proliferation and differentiation of hematopoietic stem progenitor cells with the genome. For example, smarca5 deletion affects the binding of SPI1 in the promoter region of bcl-11ab, resulting in the down-regulation of bcl-11ab expression, which leads to the development defect of hematopoietic stem progenitor cells in CHT region. This study reveals the importance of epigenetic regulation in the development of hematopoietic stem progenitor cells at different stages in various hematopoietic tissues. The research is supported by the national key R & D program, the National Natural Science Foundation of China and the Chinese Academy of Sciences. < / P > < p > note: in hematopoietic stem progenitor cells at different developmental stages, such as generation, expansion / differentiation, chromatin accessibility and transcriptome have dynamic changes, which are accompanied by the dynamic expression of chromatin remodeling factors. Among them, smarca5 promotes chromatin remodeling by interacting with nucleolin and regulates the binding of hematopoietic related transcription factors with genome, thus promoting the development of hematopoietic stem progenitor cells. For example, smarca5 deletion affects the binding of SPI1 in the promoter region of bcl-11ab, resulting in the down-regulation of bcl-11ab expression, which leads to the development defect of hematopoietic stem progenitor cells in CHT region. CUISINE&HEALTH